title: Charcot-Marie-Tooth 1B caused by expansion of a familial myelin protein zero (MPZ) gene duplication.
abstract: Charcot-Marie-Tooth (CMT) disease is a group of hereditary disorders affecting the motor and sensory nerves of the peripheral nervous system. CMT patterns of inheritance include dominant, recessive, and X-linked disorders. Charcot-Marie-Tooth disease, type 1B (CMT1B, OMIM 118200) is an autosomal dominant neuropathy caused by mutations in myelin protein zero (MPZ, OMIM 159440), a structural protein of peripheral myelin. Most causative MPZ mutations are missense sequence variants; however, recent clinical reports have described cases of CMT1B caused by increased dosage of the MPZ gene, with over-expression of the MPZ protein suspected to be causative of the disorder. We report an unusual case of early onset de novo CMT1B, caused by amplification of a familial, apparently benign, MPZ duplication.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada; Division of Genetics, Trillium Health Partners, Credit Valley Hospital, 2200 Eglinton Ave., West, Mississauga, Ontario, Canada L5M 2N1. Electronic address: marsha.speevak@trilliumhealthpartners.ca.
authors.forename: Marsha D
authors.initials: MD
authors.lastname: Speevak
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Farrell
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis* / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D056726:Genetic Association Studies; D006801:Humans; D025202:Molecular Diagnostic Techniques; D018993:Myelin P0 Protein / Q000235:genetics*
chemical_list: C560547:MPZ protein, human; D018993:Myelin P0 Protein
keywords: Charcot–Marie–Tooth disease; Copy number variant; Hypotonia; Microarray; Myelin protein zero